TY - JOUR T1 - Quantitative Structure–Cytotoxicity Relationship of 3-Styryl-2<em>H</em>-chromenes JF - Anticancer Research JO - Anticancer Res SP - 5299 LP - 5307 VL - 35 IS - 10 AU - YOSHIHIRO UESAWA AU - HIROSHI SAKAGAMI AU - MARIKO ISHIHARA AU - HAJIME KAGAYA AU - TAISEI KANAMOTO AU - SHIGEMI TERAKUBO AU - HIDEKI NAKASHIMA AU - HIDEAKI YAHAGI AU - KOICHI TAKAO AU - YOSHIAKI SUGITA Y1 - 2015/10/01 UR - http://ar.iiarjournals.org/content/35/10/5299.abstract N2 - Background: Sixteen 3-styryl-2H-chromenes were subjected to quantitative structure–activity relationship analysis based on their cytotoxicity, tumor selectivity and anti-HIV activity, in order to find their new biological activities. Materials and Methods: Cytotoxicity against four human oral squamous cell carcinoma (OSCC) cell lines, three mesenchymal and two epithelial normal oral cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Tumor-selectivity (TS) was evaluated by the ratio of the mean CC50 (50% cytotoxic concentration) against normal human oral cells to that against OSCC cell lines. Anti-HIV activity was evaluated by the ratio of CC50 to EC50 (50% cytoprotective concentration from HIV infection). Potency-selectivity expression (PSE) was determined by the ratio of TS/CC50 against OSCC. Physicochemical, structural and quantum-chemical parameters were calculated based on the conformations optimized by the LowModeMD method. Results: All 3-styryl-2H-chromene derivatives showed relatively high tumor selectivity. Especially, the compound that has a methoxy group at 7-position of the chromene ring and chlorine at 4’-position of phenyl group in styryl moiety [12] showed the highest TS and PSE values, exceeding those of resveratrol, doxorubicin and 5-FU. All compounds showed no anti-HIV activity. Among 330 chemical descriptors, 8, 74 and 16 descriptors significantly correlated to the cytotoxicity of normal and tumor cells, and tumor-specificity, respectively. Conclusion. Multivariate statistics with chemical descriptors for molecular shape and flatness may be useful for the evaluation of tumor-specificity of 3-styryl-2H-chromenes. ER -